The cytokines and micro‐environment of fracture haematoma: Current evidence

Walters, G. E.; Pountos, Ippokratis; Giannoudis, Peter V.

doi:10.1002/term.2593

Cited by 94 publications

(81 citation statements)

References 116 publications

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“…The anti-inflammatory cytokine level in rats showed that TGFβ levels were significantly higher in surgery groups than in group 1 in the later stage, and IL-10 levels were significantly higher in surgery groups than in group 1 throughout the entire process. The increase in pro-inflammatory cytokines is evident soon after injuries (6 h) and lasts usually for 24-48 h in most cases, and the duration of this reaction depends on the severity of the trauma and the basic state of the patient [27,28]. In our experiment, the inflammatory cytokines in rats' blood samples showed the similar trend as that in most clinical cases.…”

Section: Discussionsupporting

confidence: 71%

“…Additionally, ELISA analysis of inflammatory cytokines was performed to evaluate the systemic inflammation after fractures. Skeletal and tissue injuries may cause a hyper-inflammatory reaction of the immune system manifested by elevation in levels of proinflammatory cytokines, and the massive secretion of proinflammatory cytokines usually induces upregulation of anti-inflammatory cytokines such as IL-4 and regulatory cytokines such as transforming growth factor-beta (TGFbeta) and IL-10, which results in a decrease of the severity of the inflammatory reaction [27,28]. In our study, compared with group 1 (control group), the levels of the proinflammatory cytokine TNF-α and IL-1β in groups 3 and 4 were significantly higher than those in groups 1 and 2.…”

Section: Discussionmentioning

confidence: 99%

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A novel rat model of tibial fracture for trauma researches: a combination of different types of fractures and soft tissue injuries

et al. 2019

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BackgroundThe outcomes for open tibial fractures with severe soft tissue injury are still a great challenge for all the trauma surgeons in the treatment. However, most of the existing open tibial fracture models can only provide minimal soft tissue injury which cannot meet the requirement of severe trauma research. Our goal is to investigate a novel tibial fracture model providing different fractures combined with soft tissue injury for better application in trauma research.MethodsA total of 144 Sprague-Dawley rats were randomly divided into 4 groups. With group 1 as control, the other groups sustained different right tibial fractures by the apparatus with buffer disc settings either 3 mm, 10 mm, or 15 mm. X-ray and computed tomography angiography (CTA) were performed at 6 h to evaluate the fracture patterns and vascular injuries. Peripheral blood and tibialis anterior muscle were harvested at 6 h, 1 day, 3 days, 7 days, 14 days, and 28 days for ELISA and histological analysis.ResultsX-ray and μCT results indicated that different fractures combined with soft tissue injuries could be successfully provided in this model. According to OTA and Gustilo classification, the fractures and soft tissue injuries were evaluated and defined: 36 type I in group 2, 34 type II in group 3, and 36 type III in group 4. The CTA confirmed no arterial injuries in groups 1 and 2, 2 arterial injuries in group 3, and 35 in group 4. ELISA indicated that the levels of pro-inflammatory cytokines TNF-α and IL-1β were significantly higher in group 4 than in other groups, and the levels of anti-inflammatory cytokines TGF-β and IL-10 were significantly higher in surgery groups than in group 1 in later stage or throughout the entire process. HE, Masson, and caspase-3 stains confirmed the most severe inflammatory cell infiltration and apoptosis in group 4 which lasted longer than that in groups 2 and 3.ConclusionsThe novel apparatus was valuable in performing different fractures combined with soft tissue injuries in a rat tibial fracture model with high reproducibility and providing a new selection for trauma research in the future.

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Section: Discussionsupporting

confidence: 71%

Section: Discussionmentioning

confidence: 99%

A novel rat model of tibial fracture for trauma researches: a combination of different types of fractures and soft tissue injuries

et al. 2019

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“…It has been proposed that bone-fracture healing consists of 4 main phases: the inflammatory phase, soft and hard callus formation, and the remodeling phase (35). Briefly, bone healing begins immediately after fracture with the formation of a hematoma.…”

Section: Discussionmentioning

confidence: 99%

“…Briefly, bone healing begins immediately after fracture with the formation of a hematoma. The fracture hematoma is a rich medium abundant in inflammatory molecules, including IL-1b, IL-6, IL-8, IL-10, HMGB1, and TNF-a, which regulate the inflammatory response and initiate chemotaxis and cell proliferation and differentiation (8,(35)(36)(37). Many reports have investigated the relationship between osteogenic differentiation and IL-1b, IL-6, IL-8, and TNF-a (24,(38)(39)(40)(41).…”

Section: Discussionmentioning

confidence: 99%

Concentration‐dependent, dual roles of IL‐10 in the osteogenesis of human BMSCsviaP38/MAPK and NF‐κB signaling pathways

et al. 2018

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Microenvironmental conditions can influence the differentiation and functional roles of mesenchymal stem cells (MSCs). Recent studies have suggested that an inflammatory microenvironment can significantly affect the osteogenic differentiation of MSCs. Here, we show, for the first time, that IL-10 has concentration-dependent, dual roles in the osteogenesis of human bone marrow mesenchymal stem cells (hBMSCs). Low physiologic concentrations of IL-10 (0.01-1.0 ng/ml) activate the p38/MAPK signaling pathway to promote the osteogenesis of hBMSCs, but higher pathologic doses of IL-10 (10-100 ng/ml) inhibit p38/MAPK signaling by activating NF-κB, inhibiting osteogenesis. These results demonstrate that p38/MAPK and NF-κB signaling mediates the double-edged sword effect of IL-10 on hBMSCs. The osteogenic impairment was reversed at higher doses of IL-10 when cells were supplemented with the NF-κB inhibitor BAY11-7082. These data provide important insights into the regulatory effects of IL-10 on the biologic behavior of hBMSCs.-Chen, E., Liu, G., Zhou, X., Zhang, W., Wang, C., Hu, D., Xue, D., Pan, Z. Concentration-dependent, dual roles of IL-10 in the osteogenesis of human BMSCs via P38/MAPK and NF-κB signaling pathways.

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“…These include prostaglandin‐E 2 , BMP‐2, monocyte chemoattractant proteins (MCP‐1 and MCP‐3), tumour necrosis factor‐α, transforming growth factor‐β and numerous interleukins (IL‐1β, IL‐3, IL‐6, IL‐10). These factors have been shown to be crucial to bone repair in gene knockout and receptor blocking experiments that have demonstrated diminished granulation tissue formation post‐clot formation at the healing site (Walters, Pountos, & Giannoudis, ). The highly iterative wound healing process leads to the formation of granulation tissue that is slowly replaced with a more mature connective tissue rich in collagen and fibroblasts.…”

Section: Biologic Factors In Bone Formation and Regenerationmentioning

confidence: 99%

Mesenchymal stem cells and biologic factors leading to bone formation

Bartold

Gronthos

Haynes

et al. 2019

J Clinic Periodontology

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Background Physiological bone formation and bone regeneration occurring during bone repair can be considered distinct but similar processes. Mesenchymal stem cells (MSC) and associated biologic factors are crucial to both bone formation and bone regeneration. Aim To perform a narrative review of the current literature regarding the role of MSC and biologic factors in bone formation with the aim of discussing the clinical relevance of in vitro and in vivo animal studies. Methods The literature was searched for studies on MSC and biologic factors associated with the formation of bone in the mandible and maxilla. The search specifically targeted studies on key aspects of how stem cells and biologic factors are important in bone formation and how this might be relevant to bone regeneration. The results are summarized in a narrative review format. Results Different types of MSC and many biologic factors are associated with bone formation in the maxilla and mandible. Conclusion Bone formation and regeneration involve very complex and highly regulated cellular and molecular processes. By studying these processes, new clinical opportunities will arise for therapeutic bone regenerative treatments.

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The cytokines and micro‐environment of fracture haematoma: Current evidence

Cited by 94 publications

References 116 publications

A novel rat model of tibial fracture for trauma researches: a combination of different types of fractures and soft tissue injuries

A novel rat model of tibial fracture for trauma researches: a combination of different types of fractures and soft tissue injuries

Concentration‐dependent, dual roles of IL‐10 in the osteogenesis of human BMSCsviaP38/MAPK and NF‐κB signaling pathways

Mesenchymal stem cells and biologic factors leading to bone formation

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